The specific aim of this project is to employ site-directed mutagenesis of the major human histocompatibility complex molecules (class I and class II), the restricting elements on the antigen presenting or target cell, in order to explore the relationship of their structures to their functions in the immune system, as well as to define the interaction of the class II antigen with the T cell protein CD4. In this study we will examine primarily the class I HLA antigen HLA-A2, and will also commence studies of the class II HLA antigen DRl.